Anthropometric and cardio-metabolic trait variation and genetic associations in sub-Saharan Africa

The genetics of complex traits in Africa has been historically understudied, which can contribute to healthcare inequalities. Here, we present observations of 27 anthropometric, cardiovascular, and blood biomarker measurements across 2,124 individuals from sub-Saharan Africa for whom we also have dense genotype data. First, we identified trait values that differ significantly across populations and subsistence lifestyles (e.g., hemoglobin levels and height). We then identified traits with high degrees of sexual dimorphism (e.g., weight and grip strength). ADMIXTURE analyses revealed substantial population structure in our dataset, and many of the phenotypes studied here are correlated with genetic ancestry components, particularly skin color and body size traits. A variance partitioning approach further revealed traits in which much of the SNP heritability is due to polymorphisms that also contribute to differences between ancestry components. Following genomic imputation, we performed genome-wide association studies (GWASs) for all 27 traits and identified >100 independent autosomal SNPs with genome-wide significant associations for at least one trait (p < 5 × 10^-8). Many of these trait-associated variants are rare outside of Africa (minor-allele frequency [MAF] < 1%). We found that 100 kb windows surrounding the top GWAS hits from our African-ancestry cohort were enriched for trait associations in an identically sized European cohort and vice versa. We performed a more detailed analysis of height prediction from genetic data, finding that genome-wide admixture proportions predict height in Africans better than polygenic predictors based on large-scale European height GWASs.